Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation
Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation
复制标题
DOI：
10.1139/cjpp-2014-0204
复制
发表时间：
2014-09-01
影响因子：
2.1
通讯作者：
Mahmoud, Ayman M.
中科院分区：
文献类型：
--
作者：
Mahmoud, Ayman M.
食品和药物管理局不批准和撤回药物的最重要原因是肝毒性。因此，本研究旨在评价橙皮苷对环磷酰胺（CTX）诱导的Wistar大鼠肝毒性的保护作用。大鼠接受200 mg/kg体重的单次腹膜内剂量的橙皮苷，然后连续11天口服25和50 mg/kg剂量的橙皮苷。肝损害，如血清促炎细胞因子、血清转氨酶、肝脂质过氧化和一氧化氮水平显著升高所证明。因此，谷胱甘肽含量减少，抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性明显降低。此外，CYP给药可诱导过氧化物酶体增殖物激活受体γ（PPAR γ）的大幅下调以及核因子-kappa B（NF-kappa B）和诱导型一氧化氮合酶（iNOS）mRNA表达的上调。橙皮苷以剂量依赖性方式使改变的标记物恢复到几乎正常的状态。总之，橙皮苷对CYP诱导的氧化应激和导致肝毒性的炎症具有有效的保护作用。该研究表明，橙皮苷通过上调肝脏PPAR γ表达和消除炎症和氧化应激，对CYP诱导的肝毒性发挥保护作用。
The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPAR gamma) and upregulation of nuclear factor-kappa B (NF-kappa B) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPAR gamma expression and abrogation of inflammation and oxidative stress.